Preparation of cyclopropane



Patented Aug. 20, 1940 UNETEQ STATES PREPARATION OF 'CYCLOPROIPANE William A. Lott, East Orange, N. J., assignor to E. R. Squibb & Sons, New York, N. Y., a corporation of New York No Drawing. Application April 30, 1937, Serial No. 139,987

14 Claims.

This invention relates to the preparation of cyclopropane, particularly an essentially pure cyclopropane for anesthetic use. Cyclopropane is a Valuable general anesthetic, producing surgical anesthesia with comparative safety even at high levels of muscular relaxation and in extended surgical procedures, giving fairly short and uneventful induction and recovery periods.

Cyclopropane is a cyclic hydrocarbon having the structural formula It has been prepared heretofore by two types of reactions, namely (1) by the reduction of trimethylene dihalides with zinc in aqueous alcohol lGustavson, J. Prakt. Chem. (2) 50, 380 (1894)]; and (2) by the Grignard method from trimethylene dibromide [Zelinsky and Gutt, Ber. 40, 3049 (1907) l or trimethylene chlorobromide [Domanitsky, J. Russ. Chem. Soc. 47, 1791 (1915)]. These procedures have been found to be unsatisfactory, the reduction method giving a very meager yield, and the Grignard method requiring the use of the specially processed Grignard ether.

It is an object of this invention to provide an economic process of preparing cyclopropane; more specifically, an improvement of the reduction method of preparing cyclopropane such as to increase the yield and decrease the reaction time required (by minimizing the induction period and/or accelerating the reaction).

In the practice of this invention 1,3-diha1opropanes (or trimethylene dihalides) are converted into cyclopropane by treatment with a metal reduction agent in the presence of a dissolved salt of some other metal. It is believed that the catalytic effect is due to the displacement of the metal from the salt by the metal reduction agent and formation of a galvanic couple between the two metals involved, but it is not intended that this invention shall be limited by any theory of operation Among the metals that may serve as reduction agents are zinc and magnesium. These should preferably be in finely divided condition. The most effective catalytic salts are those of the non-amphoteric metals, especially iron, copper, cobalt, and nickel; but the salts of amphoteric metals-inter alia, vanadium, chromiumfand manganese-may also be used. It is desirable to employ as the reaction medium an inert solvent, especially an alcohol, say the methyl, ethyl, or isopropyl; and the alcohol is preferably diluted with water.

The cyclopropane thus prepared is suitable for anesthetic use; but any vapor impurities present may be readily removed by treating the evolved gases with an adsorbent material such as carbon.

The following examples are illustrative of the 5 invention:

Example 1 A 500 cc. three-neck flask mounted on a steam bath is equipped with efficient mechanical agitation, a two-way forced-feed system and a reflux condenser. The trimethylene dihalide and the aqueous solution of the catalytic salt are fed through the feed system at a controlled rate by means of air or nitrogen pressure, and the cyclopropane formed is led through the reflux condenser to a gasometer, where it is collected by displacement of water.

More specifically, 34.5 g. of zinc dust is added. with agitation to 110 cc. of 86% alcohol contained in this flask. After heating to gentle refluxing, 1 cc. of a 5% solution of ferric chloride is added, and trimethylene dibromide fed in dropwise (total quantity 53.3 g). The evolution of cyclopropane begins immediately; and the yield is 97% of the theoretical.

Escample 2 The procedure of Example 1 is modified by postponing addition of the catalyst. No evolution of cyclopropane occurs even five minutes after all 3 of the trimethylene dibromide has been added; but on addition of about three drops of a 5% solution of cupric sulfate, an immediate evolution of cyclopropane ensues. The yield is 94% of the theoretical.

Example 3 The procedure of Example 1 is modified by using 1 cc. of a 5% solution of cobaltous chloride as the catalyst. The yield approximates the theoretical.

Example 4 The procedure of Example 1 is modified by using 5 cc. of a 5% solution of nickel sulfate septahydrate as the catalyst. The yield is 80% of the theoretical.

Example 5 34.5 g. of zinc dust is added with agitation to 100 cc. of 86% alcohol in the reaction flask. After heating to gentle refluxing, 1 cc. of a 5% solution of manganese chloride is added. Trimethylene dibromide is then fed in dropwise, and 0.7 co. more of the catalyst solution is added after onehalf of the dibromide has been fed in. When all Yield Catalyst added Obtained Percent None .7 77. 8 5 cc. of a 5% solution of nickel sulphate septahydrateflfll 90. 7 3 cc. of a 5% solution of copper sulphate 89. 6

The invention may be variously otherwise embodied, within the scope of the appended claims.

I claim:

1. The process of preparing cyclopropane which comprises reacting a trimethylene dihalide with a metal reduction agent in the presence of a dissolved salt of a metal displaceable by the metal reduction agent.

2. The process of preparing cyclopropane which comprises reacting trimethylene dibromide with a metal reduction agent in the presence of a dissolved salt of a metal displaceable by the .ietal reduction agent.

3. The process of preparing cyclopropane which comprises reacting trimethylene dibromide with zinc in the presence of a dissolved salt of a metal clisplaceable by zinc.

4. The process of preparing cyclopropane which comprises reacting trimethylene dibromide with zinc in the presence of a dissolved salt of a non-amphoteric metal displaceable by zinc.

5. The process of preparing cyclopropane which comprises reacting trimethylene dibromide with zinc in an alcoholic reaction medium in the presence of a dissolved salt of a metal displaceable by zinc.

6. The process of preparing cyclopropane which comprises reacting trimethylene dibromide with zinc in an aqueous alcoholic medium in the presence of a dissolved salt of a metal displaceable by zinc.

'7. The process of preparing pure cyclopropane which comprises reacting a trimethylene dihalide with a metal reduction agent in the presence of a dissolved salt of a metal displaceable by the metal reduction agent, and treating the evolved gases with adsorbent carbon.

8. The process of preparing cyclopropane which comprises reacting trimethylene dibromide with zinc in the presence of a dissolved ferric salt. i

9. The process of preparing cyclopropane which comprises reacting trimethylene dibromide with zinc in the presence of a dissolved cupric salt.

10. The process of preparing cyclopropane which comprises reacting trimethylene dibromide with zinc in the presence of a dissolved nickel salt.

11. The process of preparing cyclopropane Which comprises reacting trimethylene dibromide with zinc in the presence of ferric chloride.

12. The process of preparing cyclopropane Which comprises reacting trimethylene dibromide with Zinc in the presence of cupric sulfate.

13. The process of preparing cyclopropane which comprises reacting trimethylene dibromide with zinc in the presence of nickel sulphate.

14. The process of preparing cyclopropane which comprises reacting a trimethylene dihalide with a metal reduction agent in the presence of a dissolved salt of a non-amphoterlc metal displaceable by the metal reduction agent.

WILLIAM A. LOTT. 

